Cells appear to interact with structural and regulatory molecules of the extracellular matrix by means of specific receptors. We have analyzed putative receptors for two major glycoproteins, fibronectin and collagen. A 140,000 dalton avian membrane protein complex was demonstrated to be a fibronectin receptor by three independent criteria, including binding activity, peptide and antibody-inhibition evidence, and competition for cell adhesion to fibronectin. This fibronectin receptor was localized immunologically in developing embryos. It was also found to display distinct patterns of localization depending on the migratory state of the cell. Additional modes of cell interaction with fibronectin were defined. A protein fo 45,000 daltons with a pK of 5-6 was found to be involved in fibroblast adhesion to fibronectin, but not to laminin or spreading factor/vitronectin. The process of formation of fibrils of fibronectin by cells, but not adhesion, seemed to require complex gangliosides, as shown by several approaches including the use of somatic cell variants and inhibition of fibril formation by a ganglioside-binding fragment of fibronectin. Collagen was found to modulate fibronectin-cell interactions, and a major collagen-binding protein of fibroblasts was characterized. It was shown to be a phosphoprotein of 47,000 daltons with an unusually high pK of 9.0. It was decreased after malignant transformation, accompanied by a seven-fold increase in phosphorylation. It was also found to be novel, major, heat shock-regulated protein. We propose to compare the localizations of these binding proteins in normal and transformed cells relative to each other and to intracellular cytoskeletal proteins, and to investigate their possible roles in invasion by localization and inhibition studies. We will continue biochemical characterizations of these receptors and will determine compositions, ligand specificities, and molecular organization in terms of transmembrane organization and possible cytoskeletal interaction mechanisms. Finally the regulation of these receptors will be examined in normal, transformed, and heat-stressed cells.